Field of the Invention
The present invention is generally related to molecular biology and cardiology. More specifically, it concerns methods and compositions related to inducing physiologic hypertrophy in a cell, such as a cardiac cell, in therapeutic and preventative applications. In certain embodiments it concerns Aquaporin 7 (AQP-7). In further embodiments it involve methods and compositions that alter AQP-7, such as fatty acids combinations.
Description of Related Art
Cardiac enlargement—more commonly termed cardiac hypertrophy—is a major risk factor of premature cardiovascular morbidity and mortality. In fact, cardiac hypertrophy is the best predictor of mortality. Few drugs are effective in treating the most costly endpoint of these diseases, congestive heart failure. The most commonly used treatments include digoxin, ACE inhibitors, diuretics, and β adrenergic receptor blockade.
Excessive hemodynamic workload (heart attack or high blood pressure), genetic mutations affecting sarcomeric proteins, and alterations in calcium handling proteins are some examples of stimuli that can stress the heart and induce hypertrophy. This is referred to as pathologic hypertrophy. The initial growth of the heart is a compensatory mechanism to alleviate the increased workload and to normalize wall tension. However, if the sustained stimulus is not removed, ventricular dilatation and progression to heart failure occur. The molecular pathways that control the pathologic enlargement of the heart have not yet been fully elucidated. Such molecular events may be potential therapeutic targets for preventing or reversing hypertrophy and subsequent heart failure.
An adaptive growth of the heart also occurs during normal postnatal growth or as a consequence of physical conditioning such as exercise. This physiologic hypertrophy is associated with cardiovascular benefit. Indeed, evidence suggests that physiological cardiac growth induced by exercise may protect against pathological stimuli such as pressure overload.
Burmese pythons (Python molurus) are opportunistic ambush predators, adapted to consume large meals at infrequent intervals. As a consequence, pythons exhibit a large regulatory response to the digestion process including an increase in its metabolic rate, nutrient transport and organ mass. It has been determined that the python heart can enlarge up to 60% 2 days post-feeding and it reverts to fasting size very rapidly (Secor and Diamond, 1998). Most other regulatory parameters also return to pre-feeding states. Some aspects of the hypertrophic response in the python's heart were reported by Andersen et al., (2005) These authors determined that the increased mass of the heart does not arise from an increase in the fluid content of the tissue. Moreover, the authors report an increase in the ventricular mRNA levels for cardiac myosin.
There is a need to understand the molecular mechanisms of this physiologic hypertrophy and identify factors that serve as therapeutic and preventative agents for cardiac diseases and conditions involving hypertrophy of cardiac cells.